The histogenesis of depressed adenoma of the colon has not been sufficiently investigated. Pericryptal myofibroblasts are stromal cells expressing smooth muscle actin, and are involved in the differentiation and multiplication of epithelial cells in the colonic epithelium. COX-2 has been reported to be involved in the development of colon adenoma. We studied the histogenesis of depressed adenoma of the colon by examining the relationship between the presence of pericryptal myofibroblasts and COX-2 expression. Twenty-one depressed adenomas of the colon that had been resected endoscopically between June 1998 and May 2003 (mild-moderate atypia; mean diameter, 6.7 mm) and 23 elevated adenomas that had been resected endoscopically in 2003 (mild-moderate atypia; mean diameter, 11.7 mm), were studied. We performed immunohistochemical staining using alpha-smooth muscle actin antibody to detect pericryptal myofibroblasts. We also performed immunohistochemical staining for Cox-2. Eighteen (78.3%) of the 23 elevated adenomas and six (28.6%) of the 21 depressed adenomas were positive for pericryptal myofibroblasts immunohistochemically, showing a significant difference (P<0.001). Seventeen elevated adenomas (73.9%) and eight depressed adenomas (38.1%) were positive for COX-2 expression (P=0.016). COX-2 expression was detected in the stroma, and the sites of COX-2 expression coincided with the sites of pericryptal myofibroblasts. The histogenesis of depressed adenomas differs from that of elevated adenomas. Our results suggest that a low number of pericryptal myofibroblasts and a low COX-2 expression are associated with depressed adenomas.